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Abstract

Aging is associated with cardiac and vascular β-adrenergic receptor (β-AR) dysfunction (downregulation and desensitization). This impairment may account for the reduced cardiovascular reserve occurring with age. Exercise and β-AR blockade are known to enhance β-AR responsiveness in pathologic conditions, such as hypertension, myocardial ischemia, and heart failure. The aim of this experimental study was to investigate whether these different modalities can restore β-AR signaling in the aging heart, as well. For this purpose, we used a population of 24-month-old WKY rats, divided in the following groups: 10 sedentary (Group 1), 10 trained (Group 2), and 10 sedentary treated with the selective β1-AR antagonist metoprolol for 4 wks (Group 3), plus 10 young sedentary rats (Control group). The training program consisted of a 45 min/day treadmill exercise at a speed of 17 m/min, 5 days/wk for 12 wks. Cardiac β-AR signaling was assessed by β-AR membrane density and adenylyl cyclase activity. Left ventricular (LV) contractility was assessed in vivo by measuring the maximal first derivative of LV pressure rise (LV dP/dtmax) at baseline and after infusion of isoproterenol at 0.1, 0.5, and 1.0 mg/kg/min. Peak systolic pressure (SP) and heart rate (HR) were also assessed. The data are summarized in the table⇓. Our results indicate that exercise ameliorates cardiac age-related β-AR downregulation and desensitization by increasing β-AR density and cAMP production to levels observed in young animals. The improvement in β-AR signaling is associated with a significant enhancement of LV contractility upon β-AR stimulation. Similarly, β-AR blockade has a beneficial effect on β-AR dysfunction and LV reserve of the aging heart. The results of the present study further reinforce the notion supported by several lines of recent evidence that β-blockers and exercise reverse desensitization and improve signaling/activity of β-ARs.